This invention relates to the field of microsurgery in creating pocket spaces within muscle tissue, and more particularly to creating intramyocardial pockets for the purposes of drug delivery and/or stimulation of angiogenesis of the myocardium of the heart.
Various surgical techniques have been developed to counteract ischemic conditions of the heart, including coronary bypass grafts, angioplasty and for patients who are not suitable candidates for these procedures, or in conjunction with these procedures, transmyocardial revascularization (TMR). In TMR generally, the surgeon creates many narrow channels of approximately one millimeter width that span from an opening at the endocardial surface of a ventricle of the heart, preferably the left ventricle, into the myocardium and then terminating before the epicardial surface. The surgeon generally uses laser to create the channels by either accessing the endocardium through a percutaneous route or the epicardium through an incision into the chest wall. The pressure within the left ventricle at systole forces oxygenated blood into the channels and consequently oxygenates the ischemic myocardium of the left ventricle. Methods of TMR using laser, a combination of laser and mechanical, and solely mechanical apparatus have been disclosed in the prior art, including United States patents such as U.S. Pat. Nos. 4,658,817 (Hardy), 5,125,926 (Rudko, et al) and 5,380,316 and 5,389,096 (Aita, et al) and also more recently in co-pending applications Ser. No. 08/607,782 and Ser. No. 08/713,531.
The percutaneous method does not require the epicardium to be perforated. The surgical method through incision into the chest wall does require perforation of the epicardium to create channels through the myocardium and endocardium which may result in increased peri- and post-operative bleeding. Recent methods described in pending application Ser. Nos. 08/607,782 abd 08/713,531, however, provide for initial mechanical piercing of the epicardium prior to ablation of myocardial and endocardial tissue by laser which reduces bleeding from the channels into the chest cavity.
A current limit of TMR in revascularizing myocardial tissue includes post-operative closure of a significant proportion of the channels. With little success, attempts have been made by practitioners to maintain the patency of the lumen of the channels through administration of appropriate pharmacologically active compounds. Maintaining a sufficient concentration of such compounds within the channels is very difficult considering the channels are exchanging circulation with the high blood volume interchange of the left ventricle.
TMR""s effectiveness in revascularizing ischemic myocardial tissue results not only from the introduction of oxygenated blood into the myocardium through the created channels, but through the increase in angiogenesis in the myocardial tissue surrounding the channels secondary to localized immune-mediated responses. Co-pending application Ser. No. 08/664,956 describes the advantage of creating channels and pockets intramyocardially in stimulating angiogenesis of the myocardium by using laser supplemented optionally with mechanical means. The pockets or channels do not need to be patent at the endocardial surface at creation nor remain patent over time for the angiogenesis stimulation to be effective. The stimulation of angiogenesis occurs through localized immune mediated response to the tissue trauma resulting in an influx of blood borne growth and healing factors and stimulation of capillary growth surrounding the pockets or channels. The oxygenation of myocardial tissue and the functioning capacity of the heart are thereby increased significantly. It is desireable, therefore, to provide an effective concentration of pharmacologically active angiogenic compounds to the myocardium to stimulate angiogenesis on a supplementary or independent basis for the same drug delivery problems as discussed above.
Methods have been disclosed in certain of the above cited art for removing myocardial tissue through laser emission ablation or mechanical cutting techniques to create channels and/or pockets for myocardial revascularization purposes. A noted advantage of using a mechanical cutting tool over the laser method is the ability to cut and remove a discrete piece of tissue. In addition, less bleeding occurs with the use of mechanical as verses laser perforation of the epicardium.
An advantage of using laser over the mechanical method is the reduction in force necessary to pierce the surface and advance through the body of a muscle, and more particularly, piercing the epicardium and advancing through myocardial tissue. The reduction in force allows the surgeon greater ease and control over the procedure. An additional advantage of laser over mechanical surgery is that thermal as compared to mechanical trauma of tissue results in less peri- and post-operative bleeding, less consequential tissue tearing with consequential post-operative fibrous scarring, and potentially greater post-operative immune-mediated reactive angiogenesis.
Methods have been disclosed in certain of the above cited art for synchronizing the laser emission of TMR with the heart beat (as measured by EKG) of the heart (U.S. Pat. No. 5,125,926 (Rudko, et al). These synchronization efforts were made in the attempt to time the emission of the laser with the electrically quiet period of the heart to reduce the occurence of arrhythmias. The peaks of the EKG waves reflect the electrical conductance of the heart, however, and therefore do not directly match the actual contraction of the musculature of the heart. Methods have not been disclosed for synchronizing, directly or indirectly, pocket formation with the contraction of the heart.
The above methods and apparatus and discoveries to date have not provided for concomitant administration of pharmacologically active substances to the channels and/or pockets at their creation. It is therefore desirable to provide an apparatus and method for making distinct pockets within muscle tissue, and in particular, the myocardium, for controllable drug delivery for purposes, among others, of increasing the patency of myocardial channels and/or increasing angiogenesis in the surrounding myocardial tissue. It is further desirable to provide an apparatus and method that simultaneously combines the use of laser and mechanical means to maximize the advantages and minimize the disadvantages of each. Such an apparatus and method is easily controlled by a surgeon, administers moderate thermal damage reducing reactive bleeding and fibrous scarring and increasing reactive immune-mediated localized angiogenesis, cleanly removes all excised tissue, and concomitantly optionally delivers substances or inserts containing pharmacologically active compounds into the formed pocket. It is also further desired to provide an apparatus and method for directly synchronizing the timing of the pocket formation with the contraction of the heart.
Broadly, an advantage of the present invention is to provide an apparatus and method for creating pockets within muscle tissue for purposes of stimulation and/or delivering substances containing pharmacologically active compounds.
More specifically, an advantage of the present invention is to provide an apparatus and method for creating pockets within the myocardium of the heart, for purposes of stimulation and inserting substances in the pockets that concomitantly are effective in stimulating angiogenesis in surrounding myocardial tissue and/or maintaining the patency of any nearby TMR created channels.
Another advantage of the present invention is to provide an apparatus and method for cleanly removing a distinct piece of tissue from an organ or body tissue through a mechanical punching means thus reducing the likelihood of consequential emboli.
Another advantage of the present invention is to provide an apparatus and method using a reservoir means for storing the excised tissue to allow multiple pockets to be successively created without interruption for removal of excised tissue all using the same apparatus.
Another advantage of the present invention includes providing a measurement device for setting the distance within the muscle tissue at which the tissue shall be excised.
Another optional advantage of the present invention includes providing an apparatus and method using a leading laser tip delivering low level thermal damage to reduce the force necessary for piercing of the epicardium and advancing the tool through or into the myocardium. The apparatus is thereby easier to control and manipulate by the surgeon, causes less bleeding at the epicardial surface than using a higher power laser and less fibrosis overall than using a mechanical piercing tool, and provides supplemental angiogenic stimulation by thermal damage of the myocardium.
An additional advantage of the invention is to provide an apparatus and method with a timing mechanism allowing the punching means to open and then rapidly close at the highest point of contraction at systole thereby allowing tissue to enter the gap created by the opening initially and then cutting the tissue within the gap which controls the size of tissue removed and reduces the arrhythmic side effects of removing the tissue. A further advantage is to have the timing mechanism directly reflect the contraction of the muscle by means of a pressure measurement.
A further advantage of the present invention is providing a method and apparatus for drug delivery to introduce substances with at least one pharmacologically active compound into the pockets and/or channels created. More particularly, an advantage of the invention includes providing a continuous flow drug delivery means and/or a pulsed drug delivery means where the pulsed drug delivery means introduces a bolus of substance timed and directed to release at the location and moment of pocket creation.
The present invention comprises a method and apparatus for creating pockets containing substances with pharmacologically active compounds within muscle tissue. One example of muscle tissue where the method and use of the apparatus is very applicable is ischemic myocardial tissue in need of high localized concentrations of angiogenic factors. Other examples include tumors and bone.
A mechanical excising device including a tapered dilator tip combined with an elongated flexible low-powered lasing apparatus at the dilator tip, such lasing apparatus including at least one optical fiber, is inserted via surgical incision and guided to the location exterior to the designated organ or body tissue to be treated. For example, with treating the myocardium of a ventricle of the heart, the device is inserted into the chest cavity of a patient and guided to an area exterior to the ventricle. The low-powered optical fiber lasing apparatus at the dilator tip of the device is activated and disperses low level thermal trauma upon contact thus reducing the force necessary to advance the dilator tip through the epicardium and myocardium to create a tunnel passage for the device. The thermal damage also reduces the overall bleeding in the myocardium and the tendency towards fibrosis with mechanical trauma, and increases the stimulation of angiogenesis in neighboring myocardial tissue.
The surgeon advances the excising tool to a designated distance by means of a hand-held control device. The excising tool is connected to the hand-held control device, and its attachment is secured by a trap slide means. A synchronized timing means (for example, an intramyocardial pressure detector or an EKG), optionally is synchronized with the hand-held control device to determine the opening and closing of the punching mechanism of the excising tool allowing myocardial tissue to enter the gap created by the opening and then be cut by rapid closure of the sharpened edges of the punch at maximum contraction at systole, thus creating a pocket within the tissue. The synchronized timing means preferably is a pressure detector located on the surface of the excising tool and connected with a power means for activating the punch mechanism. An insertion means within the device optionally introduces a substance, preferably containing a pharmacologically active compound, into the pocket to maintain a sufficient concentration of such a compound within the localized tissue. Such insertion means may be a continuous flow mechanism and/or be simultaneously triggered to deliver a bolus of the substance into the pocket with punch closure. For example, for intramyocardial pockets, an angiogenic compound such as VEGF may be inserted into the pockets to increase the angiogenesis within surrounding myocardial tissue. The device will then be moved within the myocardium to optionally create another intramyocardial pocket.
The advancement or withdrawal of the excising tool through the myocardium will be measured by a depth guide located on the surface of the excising tool. More particularly, the surgeon may optionally advance the excising tool through the myocardium and endocardium to the point of entry into the ventricle whereupon the surgeon will detect the significant reduction in pressure necessary to advance the tool. At this point, the surgeon may optionally withdraw the excising tool through the myocardium, creating pockets at designated depths along its path. Alternatively, the surgeon may optionally have already created pockets on the advancement of the excising tool through the myocardium, obviating the need to create pockets upon its withdrawal. The pockets are created by the Surgeon""s trigger of a release button on the hand-held control device and coordinately also based on the synchronized timing mechanism.
The excised tissue is trapped within a reservoir means within the excising tool. With closure of the punching mechanism, the trapped tissue is compressed into the reservoir. Optionally, a means of measuring the filling of the reservoir is provided on the hand-held control device. Alternatively, after a set number of punches, for example five, the surgeon may manually empty the reservoir means or the excising tool may automatically require resetting mandating an emptying of the reservoir outside the body. The reservoir means may be emptied upon complete removal of the excising tool from the chest cavity, opening of the punching mechanism, forward expulsion of the tissue out of the opening by a plunger means within the excising tool and brushing off the extruding tissue. The foregoing methods of handling the excised tissue allows for the process of creating multiple pockets for drug delivery within each channel passage of the tool through the myocardium.